Hypertonic saline infusion rant

Clinical Question

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A patient is admitted status post ischemic stroke with focal edema on CT scan. There is no concern regarding herniation. Is there a role for continuous infusion of hypertonic saline with a goal of maintaining a sustained elevation of sodium?

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Theoretical Benefit

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Theoretically, elevating the tonicity of the blood could remove water from the brain thereby decreasing edema and intracranial pressure. This reduction in intracranial pressure could improve local cerebral perfusion pressure and assist in salvaging the ischemic penumbra.

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Theoretical Harms

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(1) Continuous elevation of osmolality may have different consequences than bolus dosing, and can actually worsen cerebral edema. It is possible that damaged brain tissue with disrupted blood-brain barrier could gradually absorb sodium (rather than extrude water). In rat models of middle cerebral artery occlusion, continuous infusion of 7.5% saline has been shown to increase infarct volume (Bhardwaj 2000).

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(2) When hypertonic saline is stopped and sodium normalizes, edema may be exacerbated.

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(3) Elevating the sodium stimulates thirst and makes patients miserable. For intubated patients, thirst may contribute to discomfort and agitation, leading to increased sedative requirements and longer time on the ventilator.

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(4) Depending on local policies, hypertonic saline infusion may lead to placement of a central venous catheter with the associated risks. Additionally, if the catheter is placed in a jugular vein this could theoretically impair venous return from the brain and elevate intracranial pressure (1).

Evidence

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There are no prospective studies of hypertonic saline infusion in adult patients with ischemic stroke.

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Hauer 2011 performed a retrospective pilot study of hypertonic saline infusions in patients with severe cerebrovascular disease using a historical control group for comparison. Among patients with ischemic stroke there was no difference in mortality, number of ICP crises, or number of patients with ICP crises. There was a decrease in the number of ICP crises per patient in the hypertonic saline group. Episodes of hyponatremia occurred less frequently in the hypertonic saline group (44% in controls vs. 13% with hypertonic saline), raising a question of whether any benefit of hypertonic saline may simply result from avoidance of hyponatremia. Patients treated with hypertonic saline infusion had significantly higher cerebral perfusion pressures, which may also confound the results. This study is inconclusive due to its retrospective design and multiple confounders.

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Guidelines

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The AHA/ACC 2013 ischemic stroke guidelines don’t go into detail with regards to edema management. They recommend treatment of edema without specifying the amount of edema that merits therapy, nor the exact approach.

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Expert opinions

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Hinson 2013: “continuous infusions of osmotic agents have shown less promise than bolus dosing… In the absence of definitive evidence in humans, mannitol rescue therapy for malignant cerebral edema is the most common clinical practice.”

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Diringer 2013: “the use of continuous infusions to create a sustained hyperosmolar state should be avoided pending further study.”

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Ryu 2013: “Insufficient evidence exists to recommend pharmacologic induction of hypernatremia as a treatment for cerebral edema. The strategy of vigilant avoidance of hyponatremia is currently a safer, potentially more efficacious paradigm.”

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Conclusions

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For the management of ischemic stroke with edema, there is no evidence supporting continuous infusion of hypertonic saline. Hypertonic saline infusions are fraught with potential hazards as outlined above. This therapy should be avoided outside the setting of a randomized controlled trial pending the availability of any evidence that it is beneficial. The most logical management for most patients should focus on good supportive care, sustained adequate cerebral perfusion pressure, normoglycemia, normoxyia, and avoidance of hyponatremia.

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Similiar to the Nielsen trial of targeted temperature management, when evaluating any trial of hypertonic saline it will be essential to differentiate benefits of avoiding hyponatremia from any benefits of induced hypernatremia. Care will also be required to avoid confounding due to improved cerebral perfusion pressures resulting from the hypertonic saline infusion. Based on current evidence it appears that the best general approach may be to vigorously defend normal physiology (i.e., avoiding hyperthermia or hyponatremia).

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This post is co-authored with Ryan Clouser (@neurocritguy), an intensivist colleague who is board certified in neuro-critical care.

Notes

(1) 3% hypertonic saline probably does not need to be given via a central line (Ropper 2012).However, many hospital policies do require a central line.Image credits: http://www.freeimages.com/photo/salt-shaker-1478372